Journal of Orthopaedic Translation最新文献

{"title":"COPB1 deficiency triggers osteoporosis with elevated iron stores by inducing osteoblast ferroptosis","authors":"Yike Wang ,&nbsp;Ruizhi Zhang ,&nbsp;Aifei Wang ,&nbsp;Xiao Wang ,&nbsp;Xiongyi Wang ,&nbsp;Jiajun Zhang ,&nbsp;Gongwen Liu ,&nbsp;Kai Huang ,&nbsp;Baoshan Liu ,&nbsp;Yutong Hu ,&nbsp;Sheng Pan ,&nbsp;Xieyidai Ruze ,&nbsp;Qiaocheng Zhai ,&nbsp;Youjia Xu","doi":"10.1016/j.jot.2025.01.017","DOIUrl":"10.1016/j.jot.2025.01.017","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis (OP) is a systemic bone metabolic disease that results from an imbalance between bone formation and bone resorption. The accumulation of iron has been identified as an independent risk factor for osteoporosis. Ferroptosis, a novel form of programmed cell death, is driven by iron-dependent lipid peroxidation. Nevertheless, the precise role of ferroptosis in iron accumulation-induced osteoporosis remains uncertain.</div></div><div><h3>Methods</h3><div>We utilized proteomics and ELISA to screen key regulatory molecules related to iron accumulation in osteoporosis populations. HE staining was used to assess osteocyte changes in Hamp knockout (KO) iron accumulation mouse models. Western Blot, qPCR, ALP staining, and Alizarin Red staining were employed to explore the effects of siRNA-mediated gene knockdown on osteogenic differentiation in the MC3T3 cell line. ELISA, micro-CT, von Kossa staining, toluidine blue staining, TRAP staining, and calcein analysis were used to study the bone phenotype of conditional gene knockout mice. RNA-seq, endoplasmic reticulum activity probes, transmission electron microscopy (TEM), Western Blot, co-immunoprecipitation (Co-IP), flow cytometry, and ChIP-seq were employed to investigate the regulatory mechanisms of the target gene in osteogenic differentiation. OVX and Hamp KO mice were used to establish osteoporosis models, and AAV-mediated overexpression was employed to explore the intervention effects of the target gene on osteoporosis.</div></div><div><h3>Results</h3><div>The experiments demonstrate that iron accumulation can lead to changes in COPB1 expression levels in bone tissue. Cellular and animal experiments revealed that COPB1 deficiency reduces the osteogenic ability of osteoblasts. Transcriptome analysis and phenotypic experiments revealed that COPB1 deficiency induces ferroptosis and endoplasmic reticulum stress in cells. Further investigation confirmed that COPB1 plays a key role in endoplasmic reticulum stress by inhibits SLC7A11 transcription via ATF6. This reduces cystine uptake, ultimately inducing ferroptosis. Overexpression of COPB1 can restore osteogenic function in both cells and mice.</div></div><div><h3>Conclusion</h3><div>This study elucidated the essential role of COPB1 in maintaining bone homeostasis and highlights it as a potential therapeutic target for treating iron accumulation-related osteoporosis.</div></div><div><h3>The translational potential of this article</h3><div>Our data elucidate the critical role of COPB1 in maintaining bone homeostasis and demonstrate that COPB1 can directly promote bone formation, making it a potential therapeutic target for the future treatment of osteoporosis.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 312-328"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Importance to understand medical device regulations for accelerating clinical translation","authors":"Qing Lu ,&nbsp;Yu-Sheng Hsueh ,&nbsp;Wenxue Tong ,&nbsp;Yuantao Zhang ,&nbsp;Jiankun Xu ,&nbsp;Ling Qin","doi":"10.1016/j.jot.2025.02.002","DOIUrl":"10.1016/j.jot.2025.02.002","url":null,"abstract":"<div><div>Clinical translation of medical devices is determined by many factors and is challenging for certain countries or regions as no regulatory body is available to approve related applications. They must rely on application for regulatory bodies of other countries or regions who have independent medical device regulatory systems, while the major markets regulatory process is different. For example, considering the market size and policy orientation, mainland China may be a good option for Hong Kong research organizations. Typically, China National Medical Products Administration (NMPA) has positioned innovation as a key growth engine and implemented various mechanisms to expedite the registration, including Marketing Authorization Holder policy (MAH), as well as the setting up of the NMPA's Guangdong-Hong Kong-Macao Greater Bay Area (GBA) Branch Office, type test reform and application for securing innovation channel application. However, there are still many challenges in the transitional process for Hong Kong universities or research institutions, to set up a company in mainland and then prepare many documental files from very beginning. In the future, taking advantage of NMPA reform and seeking cooperation with the NMPA to establish an independent regulatory body in Hong Kong to be recognized by NMPA is recommended as this alone will boost innovation in life sciences and boost in Hong Kong, and have a positive impact on the commercialization of medical devices in mainland China. Such example may also be relevant for many countries or regions who are seeking medical device approval in the designated regulatory systems.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 290-297"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A perspective on reoperations after surgical treatments of degenerative lumbar diseases","authors":"Guoan Li ,&nbsp;Won Man Park ,&nbsp;Thomas Cha","doi":"10.1016/j.jot.2025.01.014","DOIUrl":"10.1016/j.jot.2025.01.014","url":null,"abstract":"<div><div>Clinical data including reoperation rates are comparable for lumbar patients after decompression-alone or decompression-with-fusion surgeries. However, there could exist different mechanisms causing complications after the two surgeries. We discussed research and technology development perspectives for improvement of the surgeries using published clinical outcome data.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 159-162"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoclast-derived apoptotic bodies accelerate the pathological progression of osteoarthritis via disturbing subchondral bone remodeling","authors":"Hongbo Ai ,&nbsp;Ce Dou ,&nbsp;Yutong Wu ,&nbsp;Dongyang Zhang ,&nbsp;Ziyang Zhang ,&nbsp;Chao Zhang ,&nbsp;Yuhang Xi ,&nbsp;Ying Qu ,&nbsp;Jiulin Tan ,&nbsp;Pengbin Yin ,&nbsp;Jianzhong Xu ,&nbsp;Shuquan Guo ,&nbsp;Fei Luo","doi":"10.1016/j.jot.2025.01.004","DOIUrl":"10.1016/j.jot.2025.01.004","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the role of osteoclast-derived apoptotic bodies (OC-ABs) in osteoarthritis (OA), specifically their impact on subchondral bone remodeling and disease progression, and to explore potential therapeutic strategies targeting OC-AB-induced pathways.</div></div><div><h3>Methods</h3><div>We utilized a mouse model of anterior cruciate ligament transection (ACLT) to simulate post-traumatic osteoarthritis (PTOA). Levels of OC-ABs were assessed in subchondral bone and correlated with OA severity. Additionally, apoptotic body-deficient MRL/lpr mice were analyzed to evaluate the direct contribution of OC-ABs to OA progression and subchondral bone remodeling. The involvement of OC-ABs in osteogenesis was further examined using mesenchymal stem cells (MSCs), with a focus on the RANKL reverse signaling pathway. The therapeutic potential of rapamycin to counteract OC-AB effects was tested.</div></div><div><h3>Results</h3><div>Increased OC-AB accumulation in subchondral bone was positively correlated with OA severity in ACLT-induced mice. Apoptotic body-deficient MRL/lpr mice demonstrated slower OA progression and maintained more stable subchondral bone architecture, indicating a pathogenic role of OC-ABs in OA. OC-ABs significantly stimulated osteogenesis in MSCs via the RANKL reverse signaling pathway. Treatment with rapamycin effectively reversed OC-AB-induced subchondral bone formation, mitigated OA progression, and inhibited the RANKL reverse signaling pathway.</div></div><div><h3>Conclusion</h3><div>OC-ABs play a critical role in exacerbating OA by promoting subchondral bone remodeling via the RANKL reverse signaling pathway. Rapamycin presents as a promising therapeutic agent capable of mitigating OC-AB-driven pathology, highlighting new avenues for targeted OA treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 108-118"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging role of macrophages in neuropathic pain","authors":"Si-Han Tong ,&nbsp;De-Lin Liu ,&nbsp;Peng Liao ,&nbsp;Sen-Yao Zhang ,&nbsp;Jian Zhou ,&nbsp;Yao Zong ,&nbsp;Chang-Qing Zhang ,&nbsp;Yi-Gang Huang ,&nbsp;Jun-Jie Gao","doi":"10.1016/j.jot.2025.01.016","DOIUrl":"10.1016/j.jot.2025.01.016","url":null,"abstract":"<div><div>Neuropathic pain is a complex syndrome caused by injury to the neurons, which causes persistent hypersensitivity and considerable inconvenience to the patient's whole life. Over the past two decades, the interaction between immune cells and neurons has been proven to play a crucial role in the development of neuropathic pain. Increasing studies have indicated the important role of macrophages for neuroinflammation and have shed light on the underlying molecular and cellular mechanisms. In addition, novel therapeutic methods targeting macrophages are springing up, which provide more options in our clinical treatment. Herein, we reviewed the characteristics of peripheral macrophages and their function in neuropathic pain, with the aim of better understanding how these cells contribute to pathological processes and paving the way for therapeutic approaches.</div></div><div><h3>Translational potential statement</h3><div>This review provides a comprehensive overview of the mechanisms underlying the interplay between the macrophages and nervous system during the progression of nerve injury. Additionally, it compiles existing intervention strategies targeting macrophages for the treatment of neuropathic pain. This information offers valuable insights for researchers seeking to address the challenge of this intractable pain.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 227-241"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiological trends and characteristics of osteoarthritis in China during 1990–2021","authors":"Sheng Chen ,&nbsp;Mingjue Chen ,&nbsp;Chao Chen ,&nbsp;Chao Xie ,&nbsp;Yihan Yu ,&nbsp;Zengwu Shao ,&nbsp;Guozhi Xiao","doi":"10.1016/j.jot.2025.02.006","DOIUrl":"10.1016/j.jot.2025.02.006","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to comprehensively analyze the incidence, prevalence, and disability-adjusted life years (DALYs) of osteoarthritis (OA) in China from 1990 to 2021 by age, sex, joint sites, high body mass index (BMI) and sociodemographic index (SDI).</div></div><div><h3>Methods</h3><div>Data and methodologies from the Global Burden of Diseases (GBD) Study 2021 were obtained to evaluate the burden of OA in China. This assessment was conducted by estimating the number of incident cases, prevalent cases, DALYs, and corresponding age-standardized rates (ASRs). The estimated annual percentage change was employed to delineate the trends over time.</div></div><div><h3>Results</h3><div>In China, the number of OA incidence cases, prevalence cases, and DALYs increased to 11.65 million, 152.85 million and 5.33 million in 2021, respectively, exhibiting a consistent upward trend over the years. The ASRs of OA incidence, prevalence, and DALYs rose 13.86 %, 14.34 %, and 16.23 % from 1990 to 2021, respectively, with knee OA most affected. In 2021, OA incidence, prevalence, and DALYs were higher in women than in men, and increased with age for both sexes, peaking at ages 50–54 for incidence and 55–59 for prevalence and DALYs. DALYs of OA attributed to high BMI increased rapidly, and high BMI contributed to 21.64 % of the total age-standardized DALYs rate of OA in China. Positive correlations were observed between ASRs and China's SDI from 1990 to 2021.</div></div><div><h3>Conclusion</h3><div>OA constitutes a significant public health challenge in China, with a persistently high disease burden. There is a pressing need to enhance public understanding of the risk factors associated with OA and to promote preventive strategies to mitigate the future burden of this disorder.</div><div>The translational potential of this article China has the largest elderly population and the highest prevalence of OA globally. Updating and analyzing epidemiological data of OA in China will offer the public, healthcare professionals, and policymakers the most current, comprehensive, and comparable information, which holds significant translational potential.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 218-226"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Piezo1 in bone marrow stem cells in response to elevated intraosseous pressure on regulating osteogenesis and angiogenesis of steroid-induced osteonecrosis of the femoral head","authors":"Zilin Li ,&nbsp;Lizhi Han ,&nbsp;Bo Wang ,&nbsp;Ping Wang ,&nbsp;Yuxi Wang ,&nbsp;Ruoyu Wang ,&nbsp;Xiao Lv ,&nbsp;Yong Feng","doi":"10.1016/j.jot.2025.01.008","DOIUrl":"10.1016/j.jot.2025.01.008","url":null,"abstract":"<div><h3>Objectives</h3><div>Steroid-induced osteonecrosis of the femoral head (SONFH) remains a significant global health issue, with an unclear pathogenesis. Elevated intraosseous pressure is considered a key initiating factor in SONFH development. Impaired osteogenesis and angiogenesis are believed to be critical in SONFH progression. Piezo1, a mechanosensitive cation channel, may sense changes in intraosseous pressure. In this study, we set out to explore the role of Piezo1 in SONFH and how to target Piezo1 to treat SONFH.</div></div><div><h3>Methods</h3><div>Femoral head tissue specimens were collected from patients with ONFH and femoral neck fracture. Histological staining, Western blotting, and RT-PCR analysis were conducted to investigate the relationship between elevated intraosseous pressure and SONFH in rat models. Immunofluorescence staining of femoral head tissues was performed to study the spatiotemporal relationship between elevated intraosseous pressure and angiogenesis, osteogenesis, and development of SONFH.</div></div><div><h3>Results</h3><div>In the early stages of SONFH, elevated intraosseous pressure increased angiogenesis and osteogenesis. However, as the pressure continued to rise, both processes were inhibited. Furthermore, Elevated intraosseous pressure activated the Piezo1 signaling pathway in bone marrow stem cells. Piezo1 activation led to increased intracellular calcium influx, thus enhancing osteogenesis and angiogenesis through CAM-NFAT1 signaling pathway.</div></div><div><h3>Conclusion</h3><div>In the early stages of SONFH, Piezo1 in BMSCs senses increased intraosseous pressure, promoting angiogenesis and osteogenesis. Targeting Piezo1 to promote the osteogenic and angiogenic potential of stem cells, which could curb further increases in pressure, contribute to early treatment of SONFH.</div></div><div><h3>The translational potential of this article</h3><div>Currently, many mechanisms of the impact of elevated intraosseous pressure on osteonecrosis of the femoral head are still in the basic theoretical research stage, and we hope to translate them into clinical applications as soon as possible. We discovered that targeting Piezo1 curb further increases in intraosseous pressure, alleviating the damaging effects of glucocorticoids on stem cells and blood vessels, which exerting great significance in treatment of early stage SONFH.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 278-289"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of metabolic status with all-cause mortality among individuals with osteoarthritis: A prospective cohort study","authors":"Hao Yang ,&nbsp;Muhui Zeng ,&nbsp;Tianxiang Fan ,&nbsp;Haowei Chen ,&nbsp;Xiaofeng Fang ,&nbsp;Zhong Alan Li ,&nbsp;Xiaoshuai Wang ,&nbsp;David J. Hunter ,&nbsp;Changhai Ding ,&nbsp;Zhaohua Zhu","doi":"10.1016/j.jot.2025.02.004","DOIUrl":"10.1016/j.jot.2025.02.004","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Individuals with osteoarthritis (OA) often experience significant changes in their metabolic status and have a higher risk of mortality compared to the general population. However, no study has quantified the metabolic status of OA patients. Moreover, the association between metabolic status and risk of mortality among OA patients remains unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The analysis included baseline populations with OA from the UK Biobank (UKBB) study and the National Health and Nutrition Examination Survey (NHANES) 1999–2018. Metabolic status was assessed using composite scores based on body mass index, waist-hip ratio, blood pressure, fasting plasma glucose, hemoglobin A1c, C-reactive protein, triacylglycerols, and lipoproteins. Restricted cubic splines were used to define healthy ranges for each indicator regarding mortality risk. Factors received 1 if within a healthy range, else 0. Total scores ranged from 0 to 7, with 3+ indicating good metabolic health. The traditional metabolic syndrome criteria (ATP III) and the Strict definition were used for comparison. Associations between metabolic unhealth and mortality were examined using Cox proportional hazards models. Integrated Discrimination Improvement (IDI) evaluated discriminatory capacity, and Net Reclassification Improvement (NRI) assessed reclassification performance in predicting ten-year mortality.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Among 44,302 UKBB OA participants, 36.0 % were metabolically unhealthy (scores: 0–2), while in 5233 NHANES OA participants, 39.1 % were metabolically unhealthy based on our newly-established definition. After adjustment for covariates, metabolically unhealthy individuals had significantly higher all-cause mortality risk (HR: 1.36; 95 % CI: 1.26–1.47 in UKBB; HR: 1.16; 95 % CI: 1.03–1.30 in NHANES) compared to metabolically healthy individuals. In UKBB, compared to ATP III definition, the changes in IDI and NRI for our newly-established definition were 0.10 % (0.01 %, 0.20 %) and 10.60 % (1.8 %, 13.60 %), respectively. When the comparison was made with the Strict definition, the newly-established definition showed changes in IDI and NRI of 0.18 % (0.10 %, 0.20 %) and 12.10 % (10.30 %, 13.80 %), respectively. results.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;A new definition for quantifying metabolic unhealth in OA was proposed. It identified a significant mortality risk with poorer metabolic status and outperformed general definitions in predictive accuracy. conclusion.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;OA is the leading joint disease worldwide, carrying a heavy health burden. Our newly established definition, evaluating metabolic health through waist-to-hip ratio, BMI, blood pressure, glucose, lipids, and C-reactive protein, identified 36.0 % OA patients in UK Biobank and 39.1 % OA patients in NHANES as having poor metabolic status, which is applicable in clinical and resea","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 207-217"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of ERK1/2 mediated activation of Drp1 alleviates intervertebral disc degeneration via suppressing pyroptosis and apoptosis in nucleus pulposus cells","authors":"Shenkai Su ,&nbsp;Xuanzhang Wu ,&nbsp;Bin Li ,&nbsp;Fengyu Zhang ,&nbsp;Kaiying Zhang ,&nbsp;Hui Wang ,&nbsp;Yan Lin ,&nbsp;Jiaoxiang Chen","doi":"10.1016/j.jot.2025.01.013","DOIUrl":"10.1016/j.jot.2025.01.013","url":null,"abstract":"<div><h3>Objective</h3><div>Dynamin-related protein 1 (Drp1) plays a crucial role in various inflammatory and degenerative diseases, yet its involvement in intervertebral disc degeneration (IVDD) remains poorly understood. This study aims to elucidate the mechanism by which Drp1 contributes to IVDD and to identify the efficacy of the Drp1 inhibitor Mdivi-1 on IVDD.</div></div><div><h3>Methods</h3><div>Tert-butyl hydroperoxide (TBHP) is utilized to induce an oxidative stress microenvironment <em>in vitro</em>. <em>In vivo</em>, IVDD model is constructed in 8-week old rats through puncture operation. The therapeutic effect of Mdivi-1 is evaluated through X-ray, MRI and histological analysis. A comprehensive set of experiments, including single-cell sequencing analysis, western blot, flow cytometry and immunofluorescence staining, are conducted to investigate the role and underlying mechanisms of Drp1 <em>in vitro</em>.</div></div><div><h3>Results</h3><div>Our study demonstrates that the expression of Drp1 and phosphorylated Drp1 (p-Drp1) are up-regulated in degenerative nucleus pulposus cells (NPCs), which are accompanied with increased pyroptosis and apoptosis. <em>In vivo</em>, both si-Drp1-mediated Drp1 knockdown and the pharmacological inhibitor Mdivi-1 alleviate puncture-induced IVDD in rats. <em>In vitro</em>, si-Drp1 or Mdivi-1 inhibits mitochondria-dependent apoptosis and pyroptosis triggered by TBHP. Mechanistically, Mdivi-1 reduces p-Drp1 levels, inhibits excessive mitochondrial fission, and mitigates mitochondrial dysfunction. Drp1 phosphorylation-based Drp1 mitochondrial translocation and subsequent apoptosis and pyroptosis are regulated by ERK1/2 phosphorylation in NPCs under oxidative stress condition.</div></div><div><h3>Conclusion</h3><div>This study highlights the involvement of Drp1 in the pathological progression of degenerative NPCs in IVDD, which is regulated by ERK1/2. Pharmacological inhibition of Drp1 with Mdivi-1 protects NPCs by promoting mitochondrial function and attenuating apoptosis and pyroptosis. These findings suggest that Mdivi-1 is a promising therapeutic candidate for IVDD treatment.</div></div><div><h3>Translational Potential</h3><div>By offering experimental evidence on the role and mechanism of Drp1 in IVDD, this study underscores the potential of Mdivi-1 as a therapeutic strategy for IVDD.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 163-175"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hip joint-preserving strategies for treating osteonecrosis of the femoral head: From nonoperative to operative procedures","authors":"Tanqiu Qi ,&nbsp;Yan Yan ,&nbsp;William Qi ,&nbsp;Weiheng Chen ,&nbsp;Haisheng Yang","doi":"10.1016/j.jot.2025.02.001","DOIUrl":"10.1016/j.jot.2025.02.001","url":null,"abstract":"<div><div>Osteonecrosis of the femoral head (ONFH) has an exceedingly high prevalence and disability rate, causing a tremendous socioeconomic burden. The prevalence of ONFH is increasing, while the population of the patients with ONFH is becoming younger. Once the femoral head collapses, treatment becomes difficult and often requires a hip joint replacement, which is not favorable for young patients. Therefore, hip joint-preserving treatments at an early stage of ONFH are particularly important. This study provides a comprehensive review on hip-preserving strategies for treating ONFH, including nonoperative treatments (e.g., protective weight bearing, hyperbaric oxygen, pulsed electromagnetic, extracorporeal shockwave, bisphosphonate, anticoagulants, hypolipidemics, vasodilators, and traditional Chinese medicine) and operative treatments (e.g., core decompression, osteotomy, bone grafting, mesenchymal stem cell transplantation, tantalum rods, and tissue engineering). Nonoperative treatments aim to slow down the progression of the disease and delay the need for joint replacement; however, they usually cannot effectively prevent the progression of the disease, except in cases of small necrosis areas (&lt;10 %). Additionally, nonoperative treatments have unclear mechanisms that require further investigation. In contrast, operative treatments may stop the negative outcomes of necrosis and therefore appear to be more promising. Currently, an emerging area in operative treatments is regenerative medicine, which could promote the generation of bone tissues and blood vessels and restore hip joint function to pre-necrotic levels as much as possible. This review seeks to not only provide an important reference for clinicians when choosing appropriate strategies for treating ONFH but also offer certain guidance for future basic research in developing ONFH treatments.</div></div><div><h3>The translational potential of this article</h3><div>The incidence of ONFH is increasing, and patients are becoming younger on average. Therefore, the development of hip joint-preserving strategies to treat ONFH at earlier stages is urgently needed, particularly for young patients. However, a comprehensive review is lacking regarding the currently-available hip joint-preserving strategies and their effectiveness. This study is motivated to fill this gap and serve as an important reference for clinicians in choosing appropriate strategies to treat ONFH.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 256-277"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}